Serum tRF-33-RZYQHQ9M739P0J as a novel biomarker for auxiliary diagnosis and disease course monitoring of hepatocellular carcinoma

Xian Li; Yang Li; Jie Yuan; Weiwei Zhang; Tianxin Xu; Rongrong Jing; Shaoqing Ju

doi:10.1016/j.heliyon.2024.e30084

Serum tRF-33-RZYQHQ9M739P0J as a novel biomarker for auxiliary diagnosis and disease course monitoring of hepatocellular carcinoma

Heliyon. 2024 Apr 20;10(9):e30084. doi: 10.1016/j.heliyon.2024.e30084. eCollection 2024 May 15.

Authors

Xian Li^{1

2}, Yang Li¹, Jie Yuan^{1

2}, Weiwei Zhang², Tianxin Xu¹, Rongrong Jing², Shaoqing Ju²

Affiliations

¹ Medical School of Nantong University, Nantong, Jiangsu, 226001, China.
² Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, China.

Abstract

Objective: In most cases, patients with hepatocellular carcinoma (HCC) develop advanced disease when diagnosed. Finding new molecules to combine with traditional biomarkers is crucial for HCC early diagnosis. In cancer development, tRNA-derived small RNAs (tsRNA) play a crucial role. Here, we aimed to identify a novel biomarker among tsRNAs that can facilitate HCC diagnosis and monitor its prognosis.

Methods: We screened candidate tsRNAs in 3 pairs of HCC and adjacent tissues through high-throughput sequencing. tRF-33-RZYQQ9M739P0J was screened in tissues, sera, and cells through quantitative real-time polymerase chain reaction (qRT-PCR) for further analysis. tRF-33-RZYQHQ9M739P0J was characterized using agarose gel electrophoresis, Sanger sequencing, and nuclear and cytoplasmic RNA isolation. Experiments at room temperature and repeated freeze-thaw cycles were conducted to evaluate the detection performance of tRF-33-RZYQHQ9M739P0J. We measured the levels of differential expression of tRF-33-RZYQHQ9M739P0J in sera using qRT-PCR. We applied the chi-square test to evaluate the correlation between tRF-33-RZYQHQ9M739P0J expression levels and clinicopathological features, and assessed its prognostic value by plotting Kaplan-Meier curves. The diagnostic efficacy of tRF-33-RZYQHQ9M739P0J was evaluated using the receiver operating characteristic (ROC) curve. Finally, the downstream genes related to tRF-33-RZYQHQ9M739P0J were explored through bioinformatics prediction.

Results: tRF-33-RZYQHQ9M739P0J was highly expressed in HCC tissues and sera, and its expression was correlated with metastasis, TNM stage, BCLC stage, and vein invasion. Expression of tRF-33-RZYQHQ9M739P0J were decreased after surgery in patients with HCC. High serum tRF-33-RZYQHQ9M739P0J levels are associated with low survival rates, and they can predict survival times in patients with HCC according to the Kaplan-Meier analysis. Combining tRF-33-RZYQHQ9M739P0J with serum alpha-fetoprotein and prothrombin induced by vitamin K absence II can improve the diagnostic efficiency of HCC, suggesting its potential as a biomarker for HCC.

Conclusion: tRF-33-RZYQHQ9M739P0J may not only be a promising non-invasive marker for early diagnosis, but also a predictor of liver cancer progression.

Keywords: Biomarker; Diagnosis; Hepatocellular carcinoma; tRF-33-RZYQHQ9M739P0J; tRNA-derived small RNAs.